15 June, 2010
Volume 17, Issue 6

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Volume 17, Issue 6

On the cover: In this issue, Carretero et al. (page 547–559) employ phosphoproteomic approaches (symbolized by the Rubik cube of protein kinases) with gene expression analyses (symbolized in the background as a heat map) to identify an effective targeted combination therapy to treat metastatic KRASG12D LKB1−/− murine lung tumors. Illustration by Eric Smith, Julian Carretero, and Takeshi Shimamura, Dana-Farber Cancer Institute.

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Volume 17 Issue 6: June 14, 2010

Featured Article

Featured articles are freely available to all readers

NSAID Sulindac and Its Analog Bind RXRα and Inhibit RXRα-Dependent AKT Signaling

Hu Zhou, Wen Liu, Ying Su, Zhen Wei, Jie Liu, Siva Kumar Kolluri, Hua Wu, Yu Cao, Jiebo Chen, Yin Wu, Tingdong Yan, Xihua Cao, Weiwei Gao, Andrei Molotkov, Fuquan Jiang, Wen-Gang Li, Bingzhen Lin, Hai-Ping Zhang, Jinghua Yu, Shi-Peng Luo, Jin-Zhang Zeng, Gregg Duester, Pei-Qiang Huang, Xiao-Kun Zhang

Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their anticancer effects through cyclooxygenase-2 (COX-2)-dependent and independent mechanisms. Here, the authors report that Sulindac, an NSAID, induces apoptosis by binding to retinoid X receptor-α (RXRα). They identified an N-terminally truncated RXRa (tRXRα) in several cancer cell lines and primary tumors, which interacted with the p85α subunit of phosphatidylinositol-3-OH kinase (PI3K). Tumor necrosis factor-α (TNFα) promoted tRXRα interaction with the p85α, activating PI3K/AKT signaling. When combined with TNFα, Sulindac inhibited TNFα-induced tRXRα/p85α interaction, leading to activation of the death receptor-mediated apoptotic pathway. The authors designed and synthesized a Sulindac analog K-80003, which has increased affinity to RXRa but lacks COX inhibitory activity. K-80003 displayed enhanced efficacy in inhibiting tRXRa-dependent AKT activation and tRXRα tumor growth in animals.

On the Cover

In this issue, Carretero et al. (pages 547–559) employ phosphoproteomic approaches (symbolized by the Rubik cube of protein kinases) with gene expression analyses (symbolized in the background as a heat map) to identify an effective targeted combination therapy to treat metastatic KRASG12D LKB1–/– murine lung tumors. Illustration by Eric Smith, Julian Carretero, and Takeshi Shimamura, Dana-Farber Cancer Institute.

Next issue: July 13, 2010


Immediate Electronic Publication

Integrative Genomic Profiling of Human Prostate Cancer

Barry S. Taylor, Nikolaus Schultz, Haley Hieronymus, Anuradha Gopalan, Yonghong Xiao, Brett S. Carver, Vivek K. Arora, Poorvi Kaushik, Ethan Cerami, Boris Reva, Yevgeniy Antipin, Nicholas Mitsiades, Thomas Landers, Igor Dolgalev, John E. Major, Manda Wilson, Nicholas D. Socci, Alex E. Lash, Adriana Heguy, James A. Eastham, Howard I. Scher, Victor E. Reuter, Peter T. Scardino, Chris Sander, Charles L. Sawyers, and William L. Gerald


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